1. The Field of the Invention
The invention relates to a multiphase product for contraception based on a natural oestrogen with a synthetic progestogen.
Compared with the generic conventional ovulation-inhibiting products which have proved to be reliable and safe on wide use for a long time, this multiphase product achieves a greater contraceptive reliability over the entire duration of the cycle, improves the cyclic bleeding behaviour and minimizes or eliminates side effects such as breast tenderness, headaches, depressive moods and libido changes and the like.
2. Related Art
The patent literature discloses multiphase products based on natural oestrogens in combination with progestogens.
The patent EP 0 770 388 B1 describes a multiphase product for contraception whose first phase consists of 2 to 4 daily dose units, and each daily dose unit contains as active ingredient exclusively natural oestrogens. The second phase of the multiphase product consists of 2 groups of daily dose units with a combination of at least one natural oestrogen and at least one synthetic or natural progestogen. In this case, the first group is formed by 5 to 3 daily dose units and the second group is formed by 17 to 13 daily dose units. A third phase consists of 2 to 4 daily dose units, and each daily dose unit contains as active ingredient exclusively natural oestrogens. The daily dose unit of natural oestrogen remains constant within the phases, but falls from phase 1 to phase 3. The proportion of synthetic or natural progestogen in the second group of the second phase exceeds the proportion in the first group. A final phase consists of 2 to 4 daily dose units, and each daily dose unit contains as active ingredient a pharmaceutically acceptable placebo.
Use example 5 indicates a combination of oestradiol valerate with dienogest. In this case, in the first phase 3 daily dose units of 3 mg of oestradiol valerate, in the second phase, in the first group, 4 daily dose units of 2 mg of oestradiol valerate plus 1 mg of dienogest, in the second group of this second phase 16 daily dose units of 2 mg of oestradiol valerate plus 2 mg of dienogest and in the third phase 2 daily dose units of 1 mg of oestradiol valerate are administered. The last phase contains 3 daily dose units of pharmaceutically acceptable placebo.
It is additionally known that the contraceptive reliability of combination products derives from the effect of both components, of the oestrogen and of the progestogen.
It is also known that the ovulation-inhibitory dose requires 1.0 mg a day for dienogest—Dienogest: Präklinik und Klinik eines neuen Gestagens, edited by A. T. Teichmann, Walter de Gruyter Berlin/New York (1995), p. 101) and 2.0-3.0 mg for drospirenone (Rosenbaum P, Schmidt W, Helmerhorst F M et al., Inhibition of ovulation by a novel progestogen (drospirenone) . . . , Eur contracept. Reprod. Health Care 5: 16-24 (2000)).
Moreover, TAUBERT, H.-D. and KUHL, H. (Kontrazeption mit Hormonen, editors Taubert, H.-D. et al., Georg Thieme Verlag Stuttgart/New York (1995), p. 160) show that there is no connection whatsoever between the occurrence of irregular bleeding and low serum concentrations of the oestrogen, in this case ethinyl-oestradiol, or of the particular progestogen.